bateria_spikes.png

(image behind "ANTIVIRALS" from: http://site.germafobeplus.com/images/bateria_spikes.jpg)

--OBJECTIVES--

  • State how viruses differ from bacteria
  • Describe the different ways in which antiviral drugs work
  • Discuss the difficulties associated with solving the AIDS problem

Definitions:

  • Virus- Any of various submicroscopic non-cellular infectious particles.
  • Antiviral- a drug acting, directed at, or effective against viruses.
  • Capsid- the coiled or polyhedral structure, composed of proteins, that encloses the nucleic acid of a virus.
  • Retrovirus- a virus that contains RNA rather than DNA.
  • Micron(s)- also called micrometer, it is the millionth part of a meter.
  • Ribosome- a tiny organelle that is the site of protein manufacture within in a cell.
  • Chromosome- any of the microscopic rod-shaped structures that appear in a cell nucleus during cell division, consisting of nucleoprotein arranged into units (genes)
  • DNA- short for deoxyribonucleic acid, DNA is a macromolecule that is the main component of chromosomes and is the material that transfers genetic characteristics in all life forms.

Definitions from any of the following: Pearson Baccalaureate Higher Level Chemistry by Catrin Brown and Mike Ford, Oxford's Chemistry For The IB Diploma Standard and Higher Level Study Guide by Geoffrey Neuss, Chemistry 3rd edition written by John Green and Sadru Damji, and http://dictionary.reference.com.



Objective #1



3D_Influenza_virus.png
Image of influenza virus from: http://upload.wikimedia.org/wikipedia/commons/3/3b/3D_Influenza_virus.png
Virus
-The capsid envelopes the core. Many viruses have a viral envelope (lipid envelope in diagram), but is not necessarily found surrounding all viruses.

-A more basic structure of a virus is a central core of DNA or RNA, surrounded by a capsid of regularly packed protein units (capsomeres), each containing many protein molecules.

-The diagram to the left is a bit confusing, but the things that must be paid attention to are the capsid, the core of RNP (ribonucleic protein which contains RNA) and the neuraminidase. Neuraminidase's importance will be explained later on in the section on how antivirals work.

-Viruses can survive outside of host cells, but can only replicate by using a host cell's ribosomes. When the virus penetrates the host cell, it injects it's DNA or RNA into the cytoplasm, causing it to take over the cell. This causes the host cell to die or become seriously altered which can be seen through the symptoms of a viral infection. Then, the cell is made to produce new DNA or RNA, forming large numbers of viruses, and sending them out against other healthy cells to continue to replicate.


bacteria.jpg
image of bacteria: http://micro.magnet.fsu.edu/cells/bacteriacell.html

Bacteria
-A bacterium, in contrast to a virus, is a single cell microorganism between .3 and 2 microns in length.

-They have a cell structure, consisting of a cell wall made of polysaccharide molecules, cytoplasm within the cell membrane to break down food and build cell parts, and a single chromosome which in itself consists of a circular strand of DNA.

-Being cellular microorganisms, they reproduce using cell reproduction.

-The flagellum attached to the bacteria is used in locomotion, and the pilli on all sides of the bacterium is used to attached the bacterium to other microorganisms or objects.











Condensed Information Table
Bacteria
Viruses
Single cell microorganisms
Non-cellular infectious particles
Between 0.3 and 2.0 microns in length (microscopic)
Submicroscopic in size
Contains a single chromosome which in itself consists of a circular strand of DNA
Has a central core of DNA surrounded by a protein coat known as a capsid
Cell wall made of protein-sugar (polysaccharide) molecules
No cell wall, possible cell membrane, or lipid envelope
Cytoplasm within cell membrane to break down food and build cell parts
No cytoplasm
Reproduce using cellular reproduction
Reproduce inside the cells of living organisms using the ribosomes of the host cells




Objective #2


Before we describe how antivirals work, we must list the difficulties in treating viral infections.

List of difficulties in treating viral infections:
  1. The speed that the virus multiplies (by the time symptoms show up, the viruses are so numerous that antivirals will have little effect)
  2. Viruses cannot be targeted by antibiotics, because they lack cell structure
  3. Viruses live within host cells, and cannot be easily targeted
  4. Virus particles tend to mutate rapidly, changing their susceptibility to drugs

Ways antiviral drugs work:

  1. Alter the cell's genetic material so the virus cannot use the cell to multiply
  2. Prevent the virus from leaving the cell
--Notice that neither of these eradicate the viral infection, which is why viral infections can flare up even with effective treatment--

Examples of antivirals:


--Acyclovir--
acyclovir.gif
image of acyclovir structure: http://www.bmb.leeds.ac.uk/mbiology/ug/ugteach/icu8/antibiotics/antivirals.html
  • Applied topically to treat cold sores caused by the herpes virus
  • It's structure is similar to that of deoxyguanosine, one of the building blocks of DNA
    • Tricks the viral enzymes into using it as a building block for the viral DNA, thus preventing the virus from multiplying
  • Therefore, acyclovir works by altering the cell's genetic material so the virus cannot use the cell to multiply
  • Acyclovir's image is above, deoxyguanosine's is below... see the similarities?

88847-89-6.gif
image of deoxyguanosine: http://www.chemicalbook.com/ChemicalProductProperty_EN_CB6269667.htm


--Amantadine--
amantadine_structure.jpg
image of amantadine structure: http://www.edinformatics.com/interactive_molecules/3D/amantadine_molecule.htm


  • Amantadine is active against the influenza virus
  • Works by inhibiting the neuraminidase enzyme's active site, which prevents the virus from leaving the cell
    • Neuraminidase is an enzyme that is used by all influenza viruses to stick to the host cell wall as it leaves. By disabling the active site on neuraminidase, the virus can not stick to the cell wall to leave the cell, keeping it trapped inside the cell.



Objective #3


AIDS, standing for Acquired Immune Deficiency Syndrome, is caused by a retrovirus.

How AIDS conquers:
  • The virus invades certain types of white blood cells, known as T helper-cells.
    • T helper-cells normally activate other cells in the immune system, but when infected, they cannot, leaving the body unable to fight infection.
  • Once it invades a healthy cell, it makes viral-DNA from the RNA it has using an enzyme called reverse transcriptase.
    • Normally, cells use an enzyme called transcriptase to make RNA from a DNA template, which is the reverse of the operation that the AIDS virus carries out.
  • The viral-DNA is programmed to make more viral particles, and when the cell dies, these particles are released in vast quantities
    • Not only this, but as the cell divides, as is usual during cell reproduction, the viral-DNA is in both of the cells

Reasons why HIV is proving to be more difficult than other viruses to defeat:
  • The virus destroys T-helper cells which should be the cells defending against the virus.
  • The virus tends to mutate very rapidly, even within a patient.
    • There are thought to be more variations of HIV in a single patient than in the influenza virus worldwide in a year
  • The virus often hides within host cells, sometimes dormant, so the immune system has nothing to react to.

Drugs that can work against HIV infection:
  • Antiretroviral drugs (a class of antiviral drugs that act on retroviruses).
  • These drugs work at different stages of HIV infection.
    • Some inhibit the reverse transcriptase enzyme
    • Some block the HIV virus from latching on to cell membranes
    • Some prevent the assembly of new virus particles once the virus is inside the cell
  • While these drugs produce, at the very least, unpleasant side-effects, they have generally been able to prolong the health, and improve the quality of life among those infected.

Example of antiretrovirals:

  • AZT (zidovudine)
    • This drug inhibits the reverse transcriptase enzyme, prohibiting the cell from taking on newly created viral-DNA.
    • This was the first antiretroviral approved for use in AIDS treatment, and has generally been effective in delaying the progression of the disease.
AZT.gif
image of AZT from: http://www.mcld.co.uk/hiv/?q=AZT